Systematic Review and Metanalysis of Oncomarkers in IPF Patients and Serial Changes of Oncomarkers in a Prospective Italian Real-Life Case Series

Background: Idiopathic pulmonary fibrosis (IPF) is a severe progressive interstitial lung disease. At 5-year follow-up, 15% of IPF patients develop lung cancer, which significantly reduces the survival rate. Here we review the literature on the clinical role of oncomarkers in IPF progression, and describe the trend of routine oncomarkers in IPF patients over the longest follow-up yet reported. Materials and methods: A systematic search of the literature in PubMed was performed to find relevant studies published up to 24 September 2020. The most common oncomarkers were chosen to select papers related to pulmonary fibrosis. Then, 24 IPF patients and 25 non-IPF patients, followed at Careggi ILD Referral Centre and Siena Regional Referral Centre for ILD, were enrolled consecutively. Results: A few studies reported an association between serum oncomarkers and severity of IPF. NSE, CEA, Ca19.9, and Ca125 were higher in the IPF, than in the non-IPF, group at every follow-up (p < 0.05). Ca15.3 concentrations were higher in the IPF, than the non-IPF, group at t3 (p = 0.0080) and t4 (p = 0.0168). To improve the specificity and sensitivity of Ca15.3, a panel of biomarkers was analyzed, with the IPF group as dependent variable, and chitotriosidase, Cyfra 21.1, Ca15.3, Ca125, and Ca19.9 as independent variables. Conclusions: This study focused on the discovery of multiple biomarker signatures, such as combinations of oncomarkers, that are widely and routinely available in biochemistry laboratories. The combination of clinical parameters and biological markers could help achieve more accurate results regarding prognosis and response to treatment in IPF. Our results could pave the way for a more “personalized” medical approach to patients affected by IPF

Mortality on the Waiting List for Lung Transplantation in Patients with Idiopathic Pulmonary Fibrosis: A Single-Centre Experience

Purpose: Lung transplantation (LTX) is nowadays accepted as a treatment option for selected patients with end-stage pulmonary disease. Idiopathic pulmonary fibrosis (IPF) is characterized by the radiological and histologic appearance of usual interstitial pneumonia. It is associated with a poor prognosis, and LTX is considered an effective treatment to significantly modify the natural history of this disease. The aim of the present study was to analyse mortality during the waiting list in IPF patients at a single institution. Methods: A retrospective analysis on IPF patients (n = 90) referred to our Lung Transplant Program in the period 2001–2014 was performed focusing on patients’ characteristics and associated risk factors. Results: Diagnosis of IPF was associated with high mortality on the waiting list with respect to other diagnosis (p < 0.05). No differences in demographic, clinical, radiological data and time spent on the waiting list were observed between IPF patients who underwent to LTX or lost on the waiting list. Patients who died showed significant higher levels of pCO2 and needed higher flows of O2-therapy on effort (p < 0.05). Pulmonary function tests failed to predict mortality and no other medical conditions were associated with survival. Conclusions: Patients newly diagnosed with IPF, especially in small to medium lung transplant volume centres and in Countries where a long waiting list is expected, should be immediately referred to transplantation, delay results in increased mortality. Early identification of IPF patients with a rapid progressive phenotype is strongly needed

Cytomegalovirus Infection Is Associated with Development of Chronic Lung Allograft Dysfunction

Background Cytomegalovirus (CMV) is the major and most common opportunistic infection complicating lung transplant (LTX). The aim of this study was to analyse the epidemiological aspects of CMV infection in lung transplant patients subject to a pre-emptive anti-CMV approach and to study the impact of this infection on lung transplant outcome, in terms of onset of chronic lung allograft dysfunction (CLAD).Methods This single-centre retrospective study enrolled 87 LTX patients (median age 55.81 years; 41 females, 23 single LTX, 64 bilateral LTX). All patients were managed with a pre-emptive anti-CMV approach. The incidences of the first episode of CMV infection, 1, 3, 6 and 12 months after LTX, were 12.64%, 44.26%, 50.77% and 56.14%. A median interval of 41 days elapsed between LTX and the first episode of CMV infection. The median blood load of CMV-DNA at diagnosis was 20,385 cp/ml; in 67.64% of cases, it was also the peak value. Patients who had at least one episode had shorter CLAD-free survival. Patients who had three or more episodes of CMV infection had the worst outcome.Results CMV infection was confirmed to be a common event in lung transplant patients, particularly in the first three months after transplant. It had a negative impact on transplant outcome, being a major risk factor for CLAD. The hypothesis that lower viral replication thresholds may increase the risk of CLAD is interesting and deserves further investigation. © 2022, The Author(s)

Home Oxygen Therapy (HOT) in Stable Chronic Obstructive Pulmonary Disease (COPD) and Interstitial Lung Disease (ILD): Similarities, Differences and Doubts

This narrative paper reviews the current knowledge of Home Oxygen Therapy (HOT) in stable Chronic Obstructive Pulmonary Disease (COPD) and Interstitial Lung Disease (ILD), two major causes of Long-Term Oxygen Therapy (LTOT) prescription. There is evidence that LTOT improves survival in COPD subjects with chronic severe respiratory failure. HOT is also used to contrast exercise and sleeping hypoxemia and to improve Quality of Life (QoL) and symptoms. Ambulatory Oxygen Therapy (AOT) did not assure generalized improvements in symptoms and Quality of Life (QoL) of COPD subjects. There is short-term evidence in a real-life study that AOT may improve QoL in ILD subjects with Exercise Oxygen Desaturation (EOD) and exertional dyspnea. There are some differences between guidelines and practices, which translate into variations in characteristics and rates of ILD and COPD subjects admitted to LTOT and AOT. Indications on titration of oxygen flow and the best oxygen delivery device for optimal management of AOT in COPD and ILD subjects are often vague or lacking. More work is needed for optimizing and customizing HOT in COPD and ILD subjects

Evaluation of multiple-flows exhaled nitric oxide in idiopathic and non-idiopathic interstitial lung disease

Fractional exhaled nitric oxide (FeNO) is a non-invasive and reproducible marker of nitrosative stress and lung inflammation. More recently, FeNO has been proposed as a marker of severity of idiopathic pulmonary fibrosis (IPF) and systemic sclerosis associated ILD. AIM AND OBJECTIVES: to evaluate the role of FeNO in the diagnostic pathway of ILDs. METHODS: According to ERS guidelines for exhaled biomarkers in lung diseases, FeNO at multiple flow-rates (50-100-150 and 350 ml/s) and alveolar concentration of NO (CaNO) were collected in 60 healthy controls and 134 patients affected by ILD: 50 with IPF, 19 with fibrotic non-specific interstitial pneumonia (NSIP), 19 with chronic hypersensitivitis pneumonia (cHP) and 46 with connective tissue disease related ILD (CTD-ILD). ROC curves were performed to investigate the potential role of eNO parameters in discriminating between idiopathic and non-idiopathic ILDs. RESULTS: All ILD groups reported higher levels of FeNO 150-350 and CaNO than controls. Among ILDs, CTD-ILD showed more elevated FeNO 350 and CaNO levels than other ILD. In particular, CaNO reported the best diagnostic accuracy to discriminate CTD-ILD from idiopathic ILDs. CONCLUSIONS: Patients affected by ILD reported increased FeNO 150-350 and CaNO in respect with healthy controls, indicating a potential role of nitrosative stress in lung fibrosis. The significant difference of CaNO levels between idiopathic ILDs and CTD-ILD is interesting and may suggest that NO is also implicated in lung inflammation associated with rheumatological disease. Further evidence is necessary to establish if CaNO is worthy of attention in the differential diagnosis of ILDs.

Home Oxygen Therapy (HOT) in Stable Chronic Obstructive Pulmonary Disease (COPD) and Interstitial Lung Disease (ILD): Similarities, Differences and Doubts

This narrative paper reviews the current knowledge of Home Oxygen Therapy (HOT) in stable Chronic Obstructive Pulmonary Disease (COPD) and Interstitial Lung Disease (ILD), two major causes of Long-Term Oxygen Therapy (LTOT) prescription. There is evidence that LTOT improves survival in COPD subjects with chronic severe respiratory failure. HOT is also used to contrast exercise and sleeping hypoxemia and to improve Quality of Life (QoL) and symptoms. Ambulatory Oxygen Therapy (AOT) did not assure generalized improvements in symptoms and Quality of Life (QoL) of COPD subjects. There is short-term evidence in a real-life study that AOT may improve QoL in ILD subjects with Exercise Oxygen Desaturation (EOD) and exertional dyspnea. There are some differences between guidelines and practices, which translate into variations in characteristics and rates of ILD and COPD subjects admitted to LTOT and AOT. Indications on titration of oxygen flow and the best oxygen delivery device for optimal management of AOT in COPD and ILD subjects are often vague or lacking. More work is needed for optimizing and customizing HOT in COPD and ILD subjects

Protective activity of inhaled nonsteroidal antiinflammatory drugs on bronchial responsiveness to ultrasonically nebulized water.

Relatively high doses of oral aspirin are needed to afford a significant protective effect against the bronchial obstructive reaction to ultrasonically nebulized distilled water (UNDW) in asthmatic patients. Sodium salicylate at similar doses and indomethacin at normal dose afford no protection. The present study was undertaken to assess the protective activity of these drugs taken by inhalation. Thirteen asthmatic patients performed two UNDW challenges 20 minutes and 24 hours after inhalation of 900 mg lysine acetylsalicylate (L-ASA) or placebo. The volume of UNDW causing a 20\% fall in FEV1 (UNDW PD20) was calculated by linear interpolation on the dose-response curve. UNDW response after placebo was not significantly different from the preliminary test (PD20 4.3 +/- 0.7 and 4.1 +/- 04 ml, respectively, mean +/- SE), whereas after L-ASA, UNDW PD20 increased to 17 +/- 2.7 ml (p < 0.01 vs placebo) and remained significantly increased after 24 hours. In another group of 12 patients under the same experimental conditions, an equivalent dose of inhaled sodium salicylate caused no effect. Finally, in a third group of asthmatic patients pretreatment with inhaled indomethacin at two dose levels (6 patients, 25 mg; 10 patients, 50 mg) resulted in a significant dose-related protective effect. These findings indicate that inhaled indomethacin and especially L-ASA exert against UNDW-induced bronchoconstriction a potent protective effect, which appears to be mediated by inhibition of local prostaglandin synthesis in the airways. This fact could have therapeutic implications

Steroid-sparing effect of inhaled lysine acetylsalicylate and furosemide in high-dose beclomethasone-dependent asthma.

Inhaled lysine acetylsalicylate and furosemide exert a mutually potentiating protective activity on experimentally induced bronchoconstriction in asthma.Our purpose was to investigate the clinical effectiveness of combined treatment of asthma with inhaled lysine acetylsalicylate and furosemide.We performed a randomized, double-blind, crossover study in nine patients with chronic asthma requiring a high dose (2 mg/day) of inhaled beclomethasone for clinical control. Patients were treated with a combination of 720 mg inhaled lysine acetylsalicylate and 40 mg furosemide twice daily, or with matched placebo in addition to inhaled steroids. The dose of inhaled steroids was reduced by half every 15 days and eventually suspended unless a patient's respiratory condition worsened.During treatment with placebo, all patients had worsening of asthma at dosages of 1 or 0.5 mg/day beclomethasone (mean +/- SE, 833 +/- 83 micrograms/day). During combined treatment complete suspension of inhaled steroids in two patients and reduction to 0.5 to 0.25 mg in the remaining seven patients (mean, 250 +/- 72 micrograms/day) was achieved, with a mean reduction of 71\% +/- 7\%. Forced expiratory volume in 1 second, weekly peak expiratory flow rate, symptom score, and bronchodilator intake remained significantly better with combined treatment than with placebo.Treatment with inhaled lysine acetylsalicylate and furosemide allows a considerable sparing of inhaled steroids without significant side effects in patients with severe asthma